2015/02/06 by Vicente M. Reyes, Reyes, Vicente M.
Biochemistry, Genetics and Molecular Biology · Materials Science · #Biomolecules (q-bio.BM) #Enzyme Structure and Function #FOS: Biological sciences #Protein Interaction Studies and Fluorescence Analysis #Protein Structure and Dynamics
paper · pdf · doi:10.48550/arxiv.1505.01142
openalex publication_date 2015/02/06 · openalex created_date 2022/09/01 · openalex updated_date 2026/07/28
We describe two complementary methods to quantify the degree of burial of\nligand and/or ligand binding site (LBS) in a protein-ligand complex, namely,\nthe "cutting plane" (CP) and the "tangent sphere" (TS) methods. To construct\nthe CP and TS, two centroids are required: the protein molecular centroid\n(global centroid, GC), and the LBS centroid (local centroid, LC). The CP is\ndefined as the plane passing through the LBS centroid (LC) and normal to the\nline passing through the LC and the protein molecular centroid (GC). The\n"anterior side" of the CP is the side not containing the GC (which the\n"posterior" side does). The TS is defined as the sphere with center at GC and\ntangent to the CP at LC. The percentage of protein atoms (a.) inside the TS,\nand (b.) on the anterior side of the CP, are two complementary measures of\nligand or LBS burial depth since the latter is directly proportional to (b.)\nand inversely proportional to (a.). We tested the CP and TS methods using a\ntest set of 67 well characterized protein-ligand structures (Laskowski et al.,\n1996), as well as the theoretical case of an artificial protein in the form of\na cubic lattice grid of points in the overall shape of a sphere and in which\nLBS of any depth can be specified. Results from both the CP and TS methods\nagree very well with data reported by Laskowski et al., and results from the\ntheoretical case further confirm that that both methods are suitable measures\nof ligand or LBS burial. Prior to this study, there were no such numerical\nmeasures of LBS burial available, and hence no way to directly and objectively\ncompare LBS depths in different proteins. LBS burial depth is an important\nparameter as it is usually directly related to the amount of conformational\nchange a protein undergoes upon ligand binding, and ability to quantify it\ncould allow meaningful comparison of protein dynamics and flexibility.\n